1. Field of the Invention
A solid dispersion of N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is provided herein. Also, a pharmaceutical composition comprising a solid dispersion of N4-(4-([1,2,4]triazolo[1,5-60 ]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5dihydrooxazol -2-yl)quinazoline-4,6-diamine is provided herein.
2. Description of the State of the Art
N4-(4-([1,2,4]Triazolo[1,5-60 ]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine (also called “ARRY-380”), which has the structure:
is a selective ErbB2 (HER2) inhibitor described in WO 2007/059257, which is incorporated by reference in its entirety. N4-(4-([1,2,4]Triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine has been tested in human clinical trials for hyperproliferative diseases, particularly cancer (see Koch, Kevin. “ARRY-380: A Selective, Oral HER2Inhibitor for the Treatment of Solid Tumors.” American Association of Cancer Research 102nd Annual Meeting, Apr. 3, 2011; which may also be found at: http://www.arraybiopharma.com/_documents/Publication/PubAttachment462.pdf).
A powder-in-capsule (“PIC”) composition of N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine was prepared and administerred to patients with cancer, and the overall inter-patient variability for area under the plasma concentration-time curve (“AUC”) and maximum concentration (“Cmax”) was moderate to high.
There remains a need to prepare a pharmaceutical composition containing N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine that minimizes inter-patient variability of pharmacokinetics.